Targeted Therapeutic Approaches to Treat Advanced Kidney Cancer - Che-Kai Tsao
January 15, 2020
Che-Kai Tsao, MD, Medical Director of the Ruttenberg Treatment Center Tisch Cancer Institute, Mount Sinai Hospital, New York, New York, USA.
Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Alicia Morgans: Hi. I'm delighted to have here with me today, Dr. Kai Tsao, who is an Associate Professor of Medicine and the Medical Director of the Ruttenberg Treatment Center at the Tisch Center Institute at Mount Sinai Hospital here in New York. Thank you so much for being here with me today.
Che-Kai Tsao: Thanks for having me, Alicia.
Alicia Morgans: Of course. I know a lot of the clinical work that you do is around kidney cancer patients, and I'd love to hear about how you and Mount Sinai are thinking about helping all of the rest of us when targeting populations that may need therapeutic advances. And some of the studies that you've put together around those populations.
Che-Kai Tsao: Absolutely. For many, many years, the treatment for kidney cancer has been limited by the type of therapeutics that we've had. We know that back in the 1990s, we used to use chemotherapy. It wasn't very effective and very toxic. And for the last 15 years or so, we've used a number of targeted therapy for kidney cancer. Although a subset of patients can benefit well, eventually most patients progress, and unfortunately with this disease die when you have metastatic disease.
Fortunately, over the last three years or so, we know that a class of therapy called checkpoint inhibitors have now been approved for the treatment of metastatic kidney cancer. And particularly, we're talking about clear cell kidney cancers or closed-cell renal carcinomas, which are the predominant type of kidney cancer that we face here in the United States.
In essence, now we are almost entering an age of wealth in the sense that we have too many choices now and whether somebody with kidney cancer or stage four kidney cancer, it's a targeted therapy first. Whether they could get combination immunotherapy, maybe one immunotherapy, maybe a combination, that's all now a big controversy. But essentially, I think in our minds, the more therapeutic choices that we have for patients, the better it is for the patients because essentially, we know that cancers are very heterogeneous and all of us have these patients who respond to these novel therapeutics, particularly in combination for years and years with an excellent quality of life.
And we hope that here at Mount Sinai Hospital, as a kidney cancer program, we're hoping to bring the latest and most innovative therapeutic approach to our patients. Whether that's from a surgical perspective, whether that's from a radiation perspective. But specifically for systemic therapies, we're hoping through the availability of FDA approved therapeutics as well as clinical trials, we'll bring those therapeutics for our patients.
Alicia Morgans: Wonderful. What are some of the trials that you've designed to target some of the patients that are not necessarily the traditional clear cell patients, who have more of the therapeutics available?
Che-Kai Tsao: Yes, absolutely. For the clear cell standpoint, we have a number of studies that are either ongoing and then we have been accruing to. One of the studies that we have been accruing to is a combination first-line clear cell RCC study of cabozantinib and atezolizumab. And this is a multicenter Phase I/II study where there are multiple cohorts including those with clear cell RCC and non-clear cell RCC. And we know that more recently a number of combinations have been evaluated, including axitinib plus pembro which is not FDA approved based on its overall survival benefit. This also includes the approval of avelumab with axitinib as well based on the PFS benefit. And what we're trying to do in this clinical trial is we know that cabozantinib, which is a MET and AXL inhibitor as well as anti-VEGF activity is a very effective tyrosine kinase inhibitor by itself and we're very excited to see that for our patients who have advanced kidney cancer, particularly, that some of our patients have really derived benefit from this therapeutic approach.
And we're excited to be a part of this study and we're hoping that this study will, particularly the Phase II portion with this combination will be reported out soon because we see now there's a number of combinations that's in clinical trial for evaluation including pembrolizumab plus lenvatinib, which is another combination that's currently in clinical trials including a Phase III clinical trial. We think that in the future combination therapy will be kind of the standard of care. It already is, but there's a number of new combinations that potentially can be new standards of care.
Alicia Morgans: Absolutely and I think particularly for the non-clear cell patients in that cohort that might be a benefit given that their standard of care is not necessarily as clearly defined as the clear cell patients, so wonderful. And this is a multi-institutional trial and we'll make sure that we have the clinicaltrials.gov number associated with that listed by this video so that people can identify that and come either to Mount Sinai or to another institution if they are very, very keen to participate.
Che-Kai Tsao: Yes, absolutely. I think the other unmet need that we specifically have in the treatment of kidney cancer is really a biomarker-driven approach. We see successes for example in the non-small cell lung cancer space where they are now increasing our armamentarium of targeted therapies based on specific biomarkers. And we know that over the past years there's been a number of studies that have reported out looking at potentially gene expression of venture strategies, potentially CDAT infiltration in the tumors. Those have provided insight into the potential of having biomarkers to predict response so that we could one day reach the ultimate goal which is to perform precision medicine where personalized therapy had developed, to kind of balance therapeutic activity versus adverse effects of these therapies.
Alicia Morgans: Absolutely. I know the team at Mount Sinai is really interested in really engaging, making this sort of link between the clinic and the laboratory to identify those biomarkers that might help predict response, particularly given the landscape becoming such a crowded space.
Che-Kai Tsao: Yes. At Mount Sinai hospital we have an excellent immunology core group of scientists at Mount Sinai Hospital and we're accruing to a number of studies looking at biomarkers in predicting response to different therapeutics in kidney cancer. One of the studies we're currently planning to do is the potential of doing pre and post biopsies on patients who get potentially tyrosine kinase inhibitor therapy first followed by combination immunotherapy. We're able to now use cytometry techniques to potentially see different types of immune cells, before and after specific treatments. And in essence, by doing so, we hope to see that particular specific type of, whether it's T-cell CDA, T-cell infiltrations among other cells, for example, NK cells have been implicated to be an important cell in the immune response against cancers. We're hoping to see that such biomarker studies can help us continue to push forward as we try to develop these biomarkers, which is really, really important.
Alicia Morgans: Wonderful. If you had to give an overarching message to the viewers on your approach to kidney cancer from Mount Sinai and just your general approach, what would that be?
Che-Kai Tsao: Great. That's an excellent question, Alicia. To us, kidney cancer is a disease that we have hope. We have a good number of patients with appropriate therapies that have lived many, many years of quality of life. Which this, 10 years ago was not possible for patients. We know that a subset of patients who are treated with immunotherapies have great durable responses. We saw that in the initial nivolumab second-line studies for a clear SRCC that 10% are patients were responders, actually continue to respond at four years. And we're anxiously awaiting for the ipi/nivo study where we anticipate that a good subset of patients will continue to respond at three, four or five years and beyond.
We want to be able to tell patients there is hope. Having stage four kidney cancer is not the end, but a beginning. And potentially we can have the most effective treatments available for you so our patients could have the best quality of life possible. And really be under a treatment, an approach that's innovative as well as being able to access these therapies through clinical trials. That's really our goal at Mount Sinai.
Alicia Morgans: Absolutely. Innovation and access. These are two pillars of success that you guys have really have at the forefront of what you do. And we are always excited to hear about your innovation, your innovative strategies, and we look forward to hearing more as time goes on. Thank you so much for your time.
Che-Kai Tsao: Thank you, Alicia.